ArticleNature medicine2010
Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01509885 (Phase 3 Study of Cyproheptadine and Chlorpromazine Effects on Spasticity After Spinal Cord Injury), which is not on this map. Cited by 213 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 3 Study of Cyproheptadine and Chlorpromazine Effects on Spasticity After Spinal Cord Injury
Who cites it
213 citing papers in PubMed, 1 synthesis or guideline pooled it, 406 citations in OpenAlex.
- Brain Plasticity in Patients with Spinal Cord Injuries: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Exercise-Induced Alterations in Sympathetic-Somatomotor Coupling in Incomplete Spinal Cord Injury.Journal of neurotrauma · 2019Trial
- Serotonin affects movement gain control in the spinal cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Trial
- Effects of serotonergic medications on locomotor performance in humans with incomplete spinal cord injury.Journal of neurotrauma · 2014Trial
- Divergent modulation of clinical measures of volitional and reflexive motor behaviors following serotonergic medications in human incomplete spinal cord injury.Journal of neurotrauma · 2013Trial
- Methods to quantify pharmacologically induced alterations in motor function in human incomplete SCI.Journal of visualized experiments : JoVE · 2011Trial
- Descending Brainstem Systems Contribute to Ankle Clonus in Humans with Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Reverse engineering of motor unit discharge in multiple sclerosis reveals heterogeneity of voluntary motor commands.medRxiv : the preprint server for health sciences · 2026Article
- Spasticity and Abnormal Tone Regulation After Spinal Cord Injury: Mechanisms and the Effects of Neuromodulation.Biomedicines · 2026Review
- GABAA receptor mediated facilitation of proprioceptive afferent transmission to motoneurons is facilitated by TRPM8 channels on C-fibres that are gated by serotonin.bioRxiv : the preprint server for biology · 2026Article
- Serotonergic System-Targeted Nucleic Acid Hydrogel Coordinates Excitability Restoration and Circuit Reconstruction for Spinal Cord Injury Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Decreased Serum 5-HT: Clinical Correlates and Regulatory Role in NMJ of MG.Annals of clinical and translational neurology · 2026Article
- Immediate Consequences of a Spinal Cord Injury During Development: Unique Insights From Ex Vivo Models.Neural plasticity · 2026Review
- Involvement of the reticulospinal tract in the pathogenesis of spasticity after stroke and spinal cord injury.Frontiers in neuroscience · 2026Review
- Hyperreflexia after corticospinal tract lesion reflects 1 A afferent circuit changes not increased KCC2 hyperexcitability.Experimental neurology · 2025Article
- The Soleus H-Reflex as a Biomarker of Post-Injury Spasticity in Spinal Cord Injury: A Conceptual Pilot Study.NeuroRehabilitation · 2025Article
- Article
- KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury.The Journal of physiology · 2025Article
- Transcutaneous Spinal Stimulation Modulates Spinal Reflex Circuit Excitability in Persons with Spinal Cord Injury.Biomedicines · 2025Article
- Ionic Mechanisms Underlying Bistability in Spinal Motoneurons: Insights from a Computational Model.bioRxiv : the preprint server for biology · 2025Article
153 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons recover their ability to produce sustained muscle contractions and ultimately enables recovery of motor functions such as locomotion. However, without regulation from the brain, these sustained contractions can also cause debilitating muscle spasms. Accordingly, blocking constitutively active 5-HT2C receptors with SB206553 or cyproheptadine, in both rats and humans, largely eliminates these calcium currents and muscle spasms, providing a new rationale for antispastic drug therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.